As a method for cancer treatment, there is so-called cancer immunotherapy that enhances patient's own immunity against cancer cells to induce cancer regression. The main procedure of this cancer immunotherapy is administration of a peptide vaccine as a cancer antigen. For increased efficacy, simultaneous administration of a cancer antigen together with an adjuvant which activates dendritic cells has been proposed.
The present inventors have advanced the research on adjuvants used for cancer immunotherapy, and to date, they have found that measles viral diRNA (defective interference RNA) functions as an adjuvant and disclosed this finding in Patent Literature 1. Specifically, it is disclosed that the diRNA induces IFN-β expression in human cells and enhances the NK activity of NK cells, and that the diRNA administered with a cancer antigen epitope to cancer-bearing mice which had been established by inoculation of B16 melanoma cells, shows a marked effect on cancer regression. However, the problem has arisen that the diRNA exhibits an insufficient adjuvanticity when extracellularly administered because the extracellularly administered diRNA cannot be delivered to endosomal TLR3 (Toll-like receptor 3). Meanwhile, poly IC, which is widely known as a synthetic TLR3 ligand, exhibits a strong adjuvanticity in extracellular administration but may cause side effects, such as overproduction of cytokines (cytokine storm), and thus unfortunately cannot be applied in a clinical setting.
Aside from this, the present inventors have identified an oligo DNA that inhibits poly IC-inducible IFN-β expression mediated by TLR3, and reported that the oligo DNAs are internalized into cells via the same receptor as that for poly IC and partly colocalized with TLR3 (Non Patent Literature 1). However, Non Patent Literature 1 does not suggest that the oligo DNA is capable of delivering another nucleic acid linked thereto to endosomal TLR3, and it would have been unpredictable whether the oligo DNA described in Non Patent Literature 1 can deliver the stem-loop structured diRNA described in Patent Literature 1 to endosomal TLR3 by linking to the diRNA.